Junction for shear sensitive biological fluid paths

ABSTRACT

A biological fluid transport device comprises a cutwater at the junction of at least two blood flow paths. The cutwater is substantially straight, substantially vertical, or both. At least one of the fluid paths may be tubular, and in some embodiments all of the fluid paths are tubular. The shear sensitive fluid may be, without limitation, blood, blood-based combinations, cell culture media, cell suspensions, proteins, and microcapsule suspensions. The device may be part of an extracorporeal circuit (e.g., blood during heart-lung bypass procedures or blood processing), but it need not be. Preferred embodiments of the device include, without limitation, kinetic pumps, mass transfer devices, filters, reservoirs, and heat exchangers.

BACKGROUND

Shear sensitive fluids, including biological fluids such as blood andblood-based combinations, should not be exposed to sudden or extremechanges in pressure or temperature, impacts, vibration, or rapid changesin direction of flow. Nonturbulent flow is the preferred mode ofhandling shear sensitive fluids.

DISCLOSURE OF THE INVENTION

The invention is a biological fluid transport device comprising acutwater at the junction of at least two fluid paths or circuits, thecutwater being substantially straight, or substantially vertical, orboth. The junction is the location where a fluid path is split into twoor more paths. For example, the junction can be an outlet for fluid toleave a device or an inlet for fluid to enter a device. At least one ofthe fluid paths or circuits may be tubular, and in some embodiments allof the fluid paths or circuits are tubular. The shear sensitive fluidmay be, without limitation, blood, blood-based combinations such as"platelet gel," cell culture media, cell suspensions, proteins, andmicrocapsule suspensions. The device may be part of an extracorporealbypass circuit but it need not be. Preferred embodiments of the deviceinclude, without limitation, kinetic pumps, mass transfer devices,filters, reservoirs, heat exchangers, and blood processing systems (suchas diagnostic hemostasis management systems and blood coagulationtesting systems).

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a cross sectional schematic view of one embodiment of theinvention.

FIG. 2A is a partial cross sectional view of the embodiment of FIG. 1taken along the line 2--2.

FIGS. 2B through 2O are variations on the view of FIG. 2A.

FIG. 3 is cross sectional view of a preferred kinetic blood pumpembodiment of the invention.

FIGS. 4A through 4E are partial cross sectional views of the embodimentof FIG. 3 taken along the lines 4A--4A to 4E--4E, respectively.

FIG. 4F is a close up view of the portion of FIG. 3 within the circledesignated 4F.

FIG. 5 is a perspective view, including a cutaway portion, of anembodiment of the invention.

FIG. 6 is a log-log scatter plot of the data of Table 1.

DETAILED DESCRIPTION

Many biological fluids are shear sensitive. Examples include blood,blood-based combinations, cell culture media, cell suspensions,proteins, and microcapsule suspensions. Any feature, or otherobstruction present in the fluid flow path or circuit, can induce highshear by creating a high gradient, that is, a large change in velocityover a small area. (A fluid path is any series of locations occupied bythe fluid. A circuit is a path which forms at least a portion of aclosed loop, such as would be established with a path from a source offluid to a device, and another path from the device back to the source.Of course, multiple devices could be employed.)

Practical applications nearly always require that some or all of thefluid change direction so that it can be processed. Thus, most fluidtransport devices comprise housings and other components which presentjunctions at which the fluid may flow in more than one direction.Similarly, such devices may comprise obstructions, interfaces, edges,and the like, somewhere along the path or circuit traveled by the fluid.Between such devices, junctions in fluid tubing and tubing-basedaccessories may also create undesirable shear stress in the fluids theycarry. Examples of such junctions are in-line splitters and connectorswhich have more than one connection upstream and/or downstream of theflow path through the device; "Y" adapters and "T" adapters; manifolds,and the like.

For example, in extracorporeal bypass circuits, a bodily fluid isremoved from the body, presented to special purpose components, andreturned to the body. A common extracorporeal circuit includes devicessuch as kinetic pumps, mass transfer devices, filters, reservoirs, andheat exchangers. (Some of these components may be incorporated into thedesign of other of the components. For example, a mass transfer devicemay have an integral heat exchanger, reservoir, filter, or a combinationof any or all of them.) In the case of an extracorporeal blood circuitsuitable for heart-lung bypass surgery and/or blood processing systemsand diagnostic hemostasis management systems, the components may includebubble and membrane oxygenators, arterial filters, cardiotomyreservoirs, bubble separators, blood heat exchangers, and red blood cellwashers. Other types of blood management systems employ extracorporealblood circuits. The invention is suitable for all of these devices, bothwhen they are incorporated into an extracorporeal bypass circuit, andwhen such devices are used for biological shear sensitive fluids outsidethe context of extracorporeal bypass (e.g., blood in coagulation testingsystems, cell culture media, cell suspensions, proteins, andmicrocapsule suspensions).

FIG. 1 is a cross sectional schematic view of a common feature in ageneric device 10 which, for purposes of illustration only, is generallycircular in cross section and has a housing 11 of negligible thickness.The device includes an outlet 12 that permits some or all of the fluid(not shown) to leave the housing when the fluid is traveling in thegeneral direction indicated by flow arrows 14a-14d. The outlet 12 iscommonly tubular (for reasons not critical to the invention) and calleda "tangential outlet" since the axis of symmetry 16--16 of the outlet 12does not generally coincide with a diameter 18--18 of the generallycircular housing parallel to the flow through the tubular path 12.

Although not shown in FIG. 1, the tangential outlet 12 need not belocated so that the flow path axis 16 is exactly tangential with thegenerally circular cross-sectional profile of the housing. A relativelysmall amount of offset toward or away from the axis of symmetry 18 ofthe housing 11 is possible. Similarly, the outlet flow axis 16 and thehousing diameter 18 are commonly parallel in the cross-sectional plane,but slight deviations on the order of one to thirty degrees arepossible. Finally, the outlet flow axis 16 and the housing diameter 18are commonly coplanar in the cross-sectional plane, even if not exactlyparallel in that plane, but slight deviations on the order of one tothirty degrees are also possible. In any of these three cases, or in anycombination of two or three of the cases, minor modifications to thegeometry of the invention may be preferred to produce an embodiment ofthe invention suitable for the particular device under consideration. Inall such cases, the principles of the invention would still be employedand therefore all such embodiments are considered to be within the scopeof the invention as it is explained below.

Also, a common design technique is to introduce "draft," i.e., smalldeviations in various dimensions and/or angles, to provide adequateclearance for a molded housing to be removed from its mold. Suchdeviations are not necessarily reflected in the Figures or thisdescription; however, incorporation of draft or other similarmanufacturing techniques into a particular embodiment of the inventionis preferred and not considered to be a departure from the scope of theinvention.

Generally speaking, fluid flows along the general direction of the flowpaths 14a, 14b, 14c and 14d. Fluid then either enters the outlet 12 byfollowing flow path 14e, or remains within device 10 by following flowpath 14f. In detail, fluid flow in the vicinity of the junction of thegenerally circular main portion of the housing 11 and the outlet 12 willbe drawn or split, and thus experience shear, at or in the immediatevicinity of the junction of the main housing 11 and the outlet 12. Thisjunction comprises an edge commonly known as cutwater 20. The rate ofchange of fluid velocity at the cutwater 20 is a source of shear stressin kinetic pumps.

FIG. 2A is a partial cross sectional view of the cutwater 20 showingtogether the straight and vertical edge characteristic of the invention,although the edge could be either straight or vertical. The verticaldirection is substantially perpendicular to the primary direction offluid flow at the cutwater location. The edge is designated "straight"or "vertical" to distinguish it from the conventional edge, indicated inphantom, which can appear straight and vertical when viewed directly inthe plane of FIG. 1. The conventional edge is shown in phantom as thehalf-elliptical shape that follows naturally if outlet 12 is a rightcircular cylinder, as is conventional, and intersects circular housing11 along a generally tangential path. In the context of the invention, a"straight" cutwater or a "vertical" cutwater can have minor deviationsfrom a perfectly straight and/or perfectly vertical linear edge, as longas those deviations are not significant on the scale of the verticallength (height) of the cutwater. For example, the cutwater could bestraight or linear from end to end, but slanted slightly from verticalas shown in FIGS. 2B and 2C. FIGS. 2D through 2K show cutwaters whichhave minor curves at upper (FIGS. 2D and 2E) or lower (FIGS. 2F and 2G)points, or both (FIGS. 2H, 2I, 2J, and 2K). A slight curvature could bepresent over substantially all of the cutwater, as shown in FIGS. 2L and2M. The cutwater could have more than one linear segment, as shown inFIGS. 2N and 2O, with a slight angle between the segments. The apex ofthe angle need not be equidistant from the upper and lower points of thecutwater. Combinations of all of the above configurations are alsopossible. In all cases, the cutwater is considered to be substantiallystraight or substantially vertical or substantially straight andvertical, depending on the exact configuration chosen.

Although the above description assumes that fluid within the device 10leaves the housing 11 through the outlet 12, the invention could also bepracticed in a device in which the fluid direction was reversed. In suchan embodiment, fluid would enter through a tangential inlet, pass ajunction comprising a cutwater shaped as described above, and enter thedevice. Thus, in the broadest sense, the invention is a device forcarrying biological shear sensitive fluids, comprising a straight orvertical cutwater at a junction of at least two fluid paths or circuitswithin the device. The junction is the location where the fluid flowwithin a fluid path is split into two or more other paths.

Shear stress is the most significant contributor to hemolysis in bloodpumps. FIGS. 3 and 4A to 4E illustrate an embodiment of the inventionfor use on an otherwise conventional centrifugal blood pump. In general,such a device comprises a housing 100 having an inlet (not shown) forfluid (not shown) entering the housing 100, and a tangential outlet 110for the fluid to exit the housing 100. Within the housing 100, arotating impeller increases the angular velocity of the fluid, but theimpeller design preferably minimizes shear on the fluid. Once the fluidreaches the junction between the housing and the tangential outlet, itis exposed to the cutwater as described above. An example of such a pumpis the BioPump model BP-80 commercially available from MedtronicBio-Medicus of Minneapolis, Minn., USA.

FIG. 4A shows a straight and vertical cutwater 120. FIG. 4B shows thatthe cross sectional profile of fluid outlet 110 is preferablyrectangular (neglecting slight deviations due to draft) at a locationcommon to the volume of the main portion of housing 100 and outlet 110.This cross sectional profile gradually tapers, as seen from thesequential cross sectional views of FIGS. 4C and 4D. FIG. 4E shows thatthe tapering does not continue to the end of the outlet where the fluidexits the pump; that is, the inner diameter of fluid outlet 110 isgenerally circular when viewed in cross section at fluid outlet 110. Thetapering is a preferred embodiment that is not necessary to the practiceof the invention. Also, the cross sectional area of the outlet 110 atthe exit of the pump (FIG. 4E) is preferably greater than the crosssectional area of the outlet 110 at the junction with the main portionof the housing 100. This is to accommodate the inner diameter of tubingtypically connected to the pump at the outlet, but it is not necessaryto the practice of the invention.

While cutwater 120 reduces shear stress due to its vertical and/orstraight configuration alone, it is preferred to radius the edge. Asshown in detail in FIG. 4F, cutwater 120 has a radius of curvature inthe horizontal plane of preferably 0.001 to 0.030 inch, and mostpreferably at least 0.004 inch. The choice of radius of curvature shouldtake into account the clearance between the cutwater and the impeller.

The housing 100 may be constructed according to conventional techniquesfrom a variety of materials approved for contact with biological fluids,such as medical grade polycarbonates suitable for blood and blood-basedmixtures. A preferred material is available from the Bayer Corporationor the General Polymers Division of the Ashland Corporation under theBayer tradename MAKROLON, specifically type RX-2530-1118 (seehttp://www.ashchem.com/GP/data/1373.htm). The surface finish on surfacesof the housing 100 which contact blood is preferably SPI/SPE No. 2.Rough surfaces, scratches, scuffs, nicks, cracks, etc. should beeliminated to reduce shear stress in the fluid. The inner surface can becoated with an antithrombogenic agent not essential to the invention.

FIG. 5 shows a "2-way" connector 200 comprising a first fluid path 210and second and third fluid paths 220 and 230. The first fluid path 210can be an inlet to connector 200, with the second and third fluid paths220 and 230 being outlets. A substantially straight and/or verticalcutwater 240 is shown in the cutaway portion at the junction of thethree fluid paths circuits. Again, the conventional elliptical cutwateris shown in phantom. This could be an in-line flow connector for anotherwise conventional connection to suitable tubing, or it could be theconfiguration of an inlet or outlet on another otherwise conventionaldevice (not shown), such as a mass transfer device (such as a bubble ormembrane oxygenator), filters (such as an arterial or cardiotomyfilter), reservoirs (such as a blood or cardiotomy reservoir), and heatexchangers. The embodiment of FIG. 5 is suitable for extracorporealbypass circuit components, as well as components and circuits used forbiological shear sensitive fluids outside the context of extracorporealbypass (e.g., cell culture media, cell suspensions, proteins, andmicrocapsule suspensions). Application of the substantially straight orsubstantially vertical cutwater to "3-way" connectors, manifolds, andthe like can easily be accomplished.

The success of the invention is believed to be due to reduction ofelevated shear forces in the vicinity of the cutwater created by avortex set up by the flow over the cutwater surface. Fluid approaching acurved cutwater on the fluid outlet side follows a partially upward pathas it crosses over the cutwater back to the main chamber of the device.This movement results in a mean rotational motion, that is, a vortex.Fluid upstream of the cutwater and on the bottom portion of the vortex,that would otherwise move to the main chamber of the device, is forcedto move to the fluid outlet side of the cutwater in a turbulent motion.Turbulent motion is undesirable since it creates rapidly changingvelocity components that induce shear stress on the fluid. The inventivecutwater induces less shear stress because it reduces rate of change ofvelocity components on either side of the cutwater. The conventionalgeometry induces higher shear by generating higher levels of vorti cityas compared to the invention. Vorticity is generated as the fluid passesthe cutwater. These vortices create substantial changes in the magnitudeand direction of the fluid (i.e. change in velocity components) over agiven area. The inventive geometry reduces induced rotational forces onthe fluid and consequently reduces the compression of the fluid path.

EXAMPLES

Blood trauma caused by centrifugal pumps was measured for two sets ofpumps which varied only in the cutwater configuration in a conventionaltangential outlet. The configuration illustrated in FIGS. 2 through 4above was compared to a control group, that is, a comparative examplewhich differed only in the design of the cutwater. The comparativeexample had a cutwater identical to that of a standard commercial-gradecentrifugal blood pump designated Model Number BP80, available fromMedtronic Bio-Medicus, Inc. of Minneapolis, Minn., USA.

The in-vitro hemolysis test measured blood trauma caused by theextracorporeal centrifugal pumps. Plasma free hemoglobin levels aremeasured and reported over a four hour test duration. Free hemoglobingeneration rate (mg/dl/hour) is calculated. Hematocrit is adjusted atthe start of the test and monitored throughout the four hour testduration.

The test requires 1000 cc of fresh bovine blood less than eight hoursold. The blood is preferably washed and resuspended in saline, but thisis not required. The blood plasma had an initial plasma free hemoglobinlevel less than 25 mg/dl. The blood did not "auto" hemolyze. Thefollowing test conditions were applied:

    ______________________________________                                        Blood Flow Rate    4 liters/min ± 5%                                       Differential Pressure (P.sub.out - P.sub.in)                                                     400 mm Hg ± 20 mmHg                                     Temperature        37 C. ± 1 C.                                            Blood Volume       1000 cc ± 100 cc                                        Hematocrit         30% ± 1%                                                                   adjusted with saline solution                              ______________________________________                                    

The maximum plasma free hemoglobin increase of the control from thebaseline sample should be 10 mg/dl (milligrams per deciliter). If thenegative control does not meet this criteria, the test for the devicehemolysis is rendered invalid. Each device is tested over four hours,flowing at 4 l/minute.

Plasma free hemoglobin (mg/dL) is measured at time 0 and at 60 minuteintervals. Hematocrit is measured at time 0. Hematocrit is typically notexpected to change substantially in these in-vitro tests. Flow(Liters/min), temperature, and pressure are measured throughout thetest.

The test requires a kinetic pump, a pressure monitoring device, a flowprobe, a temperature monitoring device, a microhematocrit centrifuge, ablood bank centrifuge, a sequence of pressure reducers, a spectralphotometer, sodium chloride 0.9%, sterile, for adjusting hematocrit andanticoagulant. The design, number, and location of the pressure reducersare selected to minimize introduction of additional hemolysis. Forexample, a series of four inline reducers in the pump outlet line ispreferred.

The fluid handling circuit is a closed system, including the kineticpump, a blood reservoir bag, 4 to 5 feet of PVC tubing (3/8 inch I.D.)and plastic connectors. Hematocrit of the blood is adjusted to 30% byadding saline. Blood samples are drawn for blood trauma analysisaccording to the sampling plan.

The absolute rate of hemolysis was measured for 48 samples of a kineticpump using a housing having the configuration of FIGS. 3-4. The absolutehemolysis rates are listed in the second column of Table 1. The thirdcolumn of Table 1 shows the ratio of the hemolysis rates of the pumps ofFIGS. 3-4 to the comparative example, pumps having the cutwateridentical to that of the commercially available BP-80 pump as describedearlier. Entries of 1.00 indicate no change in hemolysis rate, withentries less than 1.00 indicating improvement and entries greater than1.00 indicating degradation in performance. Sample number 1 was omittedfrom the data analysis.

As indicated in the mean (N=47) hemolysis ratios, the improved cutwaterdesign resulted in a 22% decrease in rate of hemolysis. As shown in FIG.6, the decrease in hemolysis was present in the vast majority of casesover a range of absolute hemolysis rates from approximately 3 to 20.

                  TABLE 1                                                         ______________________________________                                        Sample         Absolute Rate                                                                            Hemolysis                                           ______________________________________                                        1              93.19*     3.53*                                               2              26.48      1.00                                                3              47.65      1.81                                                4              20.37      0.77                                                5              7.339      0.76                                                6              6.164      0.64                                                7              6.645      0.69                                                8              8.578      0.89                                                9              13.103     0.87                                                10             11.519     0.76                                                11             10.374     0.69                                                12             13.188     0.87                                                13             5.346      0.81                                                14             11.487     1.75                                                15             4.074      0.62                                                16             4.042      0.62                                                17             4.264      0.45                                                18             7.171      0.75                                                19             3.507      0.37                                                20             3.698      0.39                                                21             26.45      0.99                                                22             21.704     0.81                                                23             20.895     0.78                                                24             18.657     0.70                                                25             11.329     0.69                                                26             12.936     0.79                                                27             12.022     0.73                                                28             8.789      0.54                                                29             11.729     0.60                                                30             10.081     0.51                                                31             12.497     0.64                                                32             19.783     1.01                                                33             12.286     1.45                                                34             5.271      0.62                                                35             6.783      0.80                                                36             4.367      0.52                                                37             8.99       0.66                                                38             8.044      0.59                                                39             9.757      0.71                                                40             8.244      0.60                                                41             13.042     0.66                                                42             11.088     0.56                                                43             15.33      0.78                                                44             13.891     0.71                                                45             14.289     0.78                                                46             14.784     0.81                                                47             20.306     1.11                                                48             15.699     0.86                                                Count          47         47                                                  Mean           12.43      0.78                                                Std. Deviation 7.84       0.28                                                ______________________________________                                         *indicates data not used to calculate mean and standard deviation        

We claim:
 1. A centrifugal pump for biological shear sensitive fluids,comprising, in combination:(a) a housing having an inlet and acylindrical portion defining a first fluid path of constant radius; (b)an outlet connected to the housing and defining a second fluid path thattangentially connects to the first fluid path and has a changingcross-sectional profile as the second fluid path proceeds away from thehousing; (c) a substantially vertical cutwater at a junction of thefirst and second fluid paths; (d) within the housing, a rotatingimpeller designed to propel the fluid from the first fluid path towardthe cutwater such that fluid flows either into the second fluid path orremains in the first fluid path.
 2. A centrifugal pump for biologicalshear sensitive fluids, comprising, in combination:(a) a housing havingan inlet and a cylindrical portion defining a first fluid path ofconstant radius; (b) an outlet connected to the housing and defining asecond fluid path that tangentially connects to the first fluid path andhas a changing cross-sectional profile as the second fluid path proceedsaway from the housing; (c) a substantially straight cutwater at ajunction of the first and second fluid paths; (d) within the housing, arotating impeller designed to propel the fluid from the first fluid pathtoward the cutwater such that fluid flows either into the second fluidpath or remains in the first fluid path.
 3. The centrifugal pump ofclaim 1 or 2 in which the cutwater is both substantially straight andsubstantially vertical.
 4. The device of claim 1 or 2 in which at leastone of the fluid paths is an inlet for fluid to enter at least one otherpath.
 5. The centrifugal pump of claim 1 or 2 in which the shearsensitive fluid comprises a fluid chosen from the group consistingessentially of blood, cell culture media, cell suspensions, proteins,and microcapsule suspensions.
 6. The centrifugal pump of claim 1 or 2 inwhich the cutwater has a horizontal radius of curvature of between 0.001to 0.030 inch.
 7. The centrifugal pump of claim 2 in which the cutwaterhas a horizontal radius of curvature of at least 0.004 inch.